Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• enzyme of the Krebs cycle [25]. Therefore, NNG may be a toxin released to kill or outcompete nearby bacteria or other organisms for limited resources. In such a context, the physiological function of NnlA could be to protect bacteria from toxic NNG exposure. Alternatively, NnlA could be a promiscuous

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• produced by the marine Okeania sp. cyanobacterium. In the field, this type of cyanobacterium that produces the analog of human lethal toxin is often observed with macroalgae and shells, and, therefore, it can be a potential risk for food poisoning of fishery resources. Experimental General experimental

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• chemical defence, e.g., by toxin production [6]. With penicillin as the prime example fungal secondary metabolites have raised scientific and pharmaceutical interests for nearly one century. Today’s sequencing and bioinformatic analyses of fungal genomes revealed that the genetic potential far exceeds the

• epipolythiodioxopiperazine (ETP’s) class toxin of several fungal genera including Aspergillus, Penicillium, Trichoderma, and Leptosphaera (Figure 3) [112]. Among the ascomycetes, A. fumigatus may well be the major GT producer and the identification of its heterocyclic structure by Bell and colleagues in 1958 builds the

• , comparable to how Trichoderma virens protects cotton seedlings from its pathogen Pythium ultimum [122]. Trypacidin The spore-born toxin trypacidin (8) is a polyketide that belongs to an anthraquinone-derived class of secondary metabolites (Figure 4) [107]. In A. fumigatus, the trypacidin biosynthetic cluster

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• Memory Zimuwandeyi Manuel A. Fernandes Amanda L. Rousseau Moira L. Bode Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Private Bag 3, PO WITS, 2050, South Africa 10.3762/bjoc.17.99 Abstract Pavettamine, a plant toxin first isolated from Pavetta harborii in

• substituted methylene linkage. Biological studies have shown that this toxin is responsible for “quick disease” (gousiekte) in ruminant animals, which causes inhibition of protein synthesis in the cardiovascular organs [13]. The unique structure coupled with the biological effects of this polyamine prompted

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• -Leopoldshafen, Hermann-von-Helmholtz-Platz 1, Germany 10.3762/bjoc.17.22 Abstract The total synthesis of decarboxyaltenusin (5’-methoxy-6-methyl-[1,1’-biphenyl]-3,3’,4-triol), a toxin produced by various mold fungi, has been achieved in seven steps in a yield of 31% starting from 4-methylcatechol and 1-bromo

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• and toxin [(−)-adaline] content of A. bipunctata eggs, once the maternal and paternal aposematic phenotype had the most significant effect on egg traits if compared to the maternal responses to offspring predators. Thus, the phenotype can also contribute to the aposematic signal variation in a

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• , Supporting Information File 1). Nevertheless, X. innexi contains a tonB-homologue instead of the NUDIX-hydrolase fclA and an acyl-CoA-thioesterase instead of fclM and fclN, leading to the postulated compound Xenorhabdus lipoprotein toxin (Xlt, Figure S1, Supporting Information File 1) [27]. Furthermore

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• for ricin toxin A (RTA) inhibitors [14]. By deprotonation of the lactam NH, and conversion to the DBU salt, the pterin easily dissolves in methanol at high concentrations, unprecedented for unfunctionalized pterins. This greatly accelerated the development of a library of bioactive pterins, as it

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• fungi against plant hosts [12]. Well-known examples include the host-specific toxins victorin and T-toxin and other non-host-specific toxins such as the ophiobolins [11]. Bipolaris sorokiniana (syn. Cochliobolus sativus) has been identified as the causative agent of multiple diseases on wheat and barley

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• summer season in the highland areas of Japan (e.g., Nagano and Iwate prefectures) was isolated. The structure of a toxin produced by this organism was analyzed based on the detailed evaluation of its 2D NMR and FABMS spectra, and this compound has not been reported previously. We propose the name

• cichorinotoxin for this toxin. In conjunction with the D or L configurations of each amino acid, which were determined by Marfey’s method, we propose the structure of cichorinotoxin to be as follows: 3-hydroxydecanoyl-(Z)-dhThr1-D-Pro2-D-Ala3-D-Ala4-D-Ala5-D-Val6-D-Ala7-(Z)-dhThr8-Ala9-Val10-D-Ile11-Ser12-Ala13

• -Val14-Ala15-Val16-(Z)-dhThr17-D-alloThr18-Ala19-L-Dab20-Ser21-Val22, and an ester linkage is present between D-alloThr18 and Val22 (dhThr: 2-aminobut-2-enoic acid; Dab: 2,4-diaminobutanoic acid). Thus, the toxin is a lipodepsipeptide with 22 amino acids. The mono- and tetraacetate derivatives and two

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• )-inspired peptide [K4(C-βA-),F7,L17,P34]-hNPY, acting as NPY Y1 receptor (hY1R)-targeting peptide, to form a tubugi-1–SS–NPY disulfide-linked conjugate. The cytotoxic impacts of the novel tubugi-1–NPY peptide–toxin conjugate, as well as of free tubugi-1, and tubugi-1 bearing the thiol spacer (liberated from

• (Ewing`s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chemically transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic

• potency of the liberated tubugi-1 that, however, still bears the thiol spacer (tubugi-1-SH) was restored and up to 10-fold higher compared to the entire peptide–toxin conjugate. The conjugate shows toxic selectivity to tumor cell lines overexpressing the hY1R receptor subtype like, e.g., the hard to treat

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• associated with intercellular binding, cell–cell recognition, intracellular protein trafficking, and toxin activity [26]. Lectins typically possess high carbohydrate ligand specificity, enabling precise control over protein–target contacts and associated downstream processes. Lectins are often easily

• infections in humans, presumably through interference with lectin-associated pathogen–host adhesion [67][68]. Besides facilitation of adhesion, some bacterial lectins are also known to act as toxins. The secreted pertussis toxin, for example, is a lectin and an important virulence factor of Bordetella

• pertussis [69][70][71], the bacterial pathogen responsible for the respiratory disease pertussis, or whooping cough. While no reports exist to date, inhibiting the adhesion of the pertussis toxin to host–cell surface carbohydrates using carbohydrate ligand mimics might permit reduction of the pathogenicity

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• mycotoxins [2], a class of highly bioactive secondary metabolites that belong to the strongest known inhibitors of protein biosynthesis in eukaryotes [3]. Similarly, the sesquiterpene aristolochene (2) is the parent hydrocarbon of PR toxin [4][5] and has been used as a marker to differentiate between toxin

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• , Foodborne Toxin Detection & Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA 10.3762/bjoc.14.260 Abstract Interfering with bacterial cell-to-cell communication is a promising strategy to combat antimicrobial resistance. The natural

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• . Bacterial cultures were grown for eight hours in the presence of each compound, followed by extraction of the pyocyanin under acidic conditions [22]. This was then quantified by measurement of the OD520, which corresponds to absorption by the toxin. The results are shown in Figure 4, normalised by the

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• unconventional strategy has been provided recently by the approval of the toxin-neutralizing therapeutic antibody bezlotoxumab, which is henceforth in clinical use for pre-emptive treatment of recurring clostridial infections [10]. So, the potential of active principles, which do not kill the bacteria through

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• plasma and liver microsomes, absence of cytotoxicity, and excellent oral bioavailability in mice. 4. Direct toxin inhibition Numerous bacteria secrete toxins that are responsible for acute virulence. Various small molecule and antibody approaches target the inhibition of bacterial toxins in order to

• antagonize bacterial virulence [51]. AB toxins are widespread among species and consist of a catalytically active A-domain and one or more units of a receptor-binding domain B. The B domain is responsible for binding to a cell-surface receptor, which engages in receptor-mediated cellular uptake. The AB toxin

• . Numerous inhibitors have been developed against AB toxins, targeting toxin transcription, assembly, receptor binding and enzyme function [51]. A set of antibodies against diverse toxins has recently been approved for therapeutic use, which demonstrates the scientific and medical feasibility of entering the

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• (ATCC) were maintained in a mixture of Dulbecco’s Modified Eagle’s Medium and Ham’s F12 nutrient mixture supplemented with 5% inactivated horse serum, 10 μg mL−1 insulin, 0.02 μg mL−1 human epidermal growth factor, 0.5 μg mL−1 hydrocortisone, 0.10 μg mL−1 choleric toxin, 100 U mL−1 penicillin, and 100

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• protein importin-α at the nuclear envelope and triggers the uptake of the transcription factor NF-κB [22][23]. As second sequence we chose the NrTP sequence, which is a designed peptide coming from the rattlesnake toxin, called crotamine [3]. For both peptides, preferential accumulation within the nuclei

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• not better than its parent. In recent years the targeted delivery of cytotoxic agents has emerged as a highly promising method to tackle selectivity issues [36][37][38][39][40]. Cryptophycin-52 and many analogues lack an addressable group to conjugate the toxin to a homing device. For this reason, new

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• spore distribution [11]. Furthermore, volatiles can be used as taxonomic markers [12] and can serve as indicators for fungal toxin production, e.g., the fungal emission of the sesquiterpene hydrocarbon trichodiene points to the production of trichothecene mycotoxins [13]. Aspergillus is a well-described

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• Vajinder Kumar W. Bruce Turnbull Department of Chemistry, Akal University, Talwandi Sabo, Punjab, India School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, LS2 9JT, UK 10.3762/bjoc.14.34 Abstract Cholera is a diarrheal disease caused by a protein toxin

• released by Vibrio cholera in the host’s intestine. The toxin enters intestinal epithelial cells after binding to specific carbohydrates on the cell surface. Over recent years, considerable effort has been invested in developing inhibitors of toxin adhesion that mimic the carbohydrate ligand, with

• particular emphasis on exploiting the multivalency of the toxin to enhance activity. In this review we introduce the structural features of the toxin that have guided the design of diverse inhibitors and summarise recent developments in the field. Keywords: carbohydrate; cholera; multivalency; toxin

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• bicyclic octapeptide toxin belonging to the amatoxin family, found in Amanita Phalloides (death cap mushroom), see Figure 1 [1]. Its mechanism of action consists in the inhibition of cellular transcription by an effective blocking of RNA polymerase II, which is present in the nuclei of eukaryotic cells and

• xenograft tumors, with complete tumor regression in 90% of the cases after two injections of the α-amanitin-anti-EpCAM ADC at a dose of 100 μg/kg with respect to α-amanitin. In these two examples, the internalization of the monoclonal antibody and subsequent release of the toxin leads to the enhancement of

• , unfavorable pharmacokinetics (low tissue diffusion and low accumulation rate) and possible elicitation of immune response [6]. By conjugation to a specific cell-membrane-receptor ligand, the toxin can be delivered at the tumor site and internalized through receptor-mediated endocytosis. In 2013, Reshetnyak